Passive immunotherapy is a highly effective treatment for infectious diseases, whether they are acquired naturally or as a result of biological warfare. Human polyclonal antibodies developed and produced in quantity in transgenic animals will provide an immediate therapy to an outbreak of a biological warfare agent. Origen Therapeutics is developing transgenic chickens that will raise an antigen-specific, humoral immune response consisting of fully human polyclonal antibodies of high avidity and specificity for biodefense applications. The chief advantages of chickens over mammals for antibody production are that hens deposit large amounts of maternal antibodies in the egg yolk, a sterile and convenient package, and that chickens are routinely grown in SPF facilities. In the proposed work, a human surface IgM antibody of known specificity will be expressed in chicken B-lymphocytes in vivo. The experiments will address the ability of human IgM to drive the fundamental cellular processes required for antibody responses in the chicken, namely B cell development, proliferation in the bursa of Fabricius and migration to the periphery. This work will be proof of principle that the chicken immune system can produce human antibodies in its B-lymphocytes and that human antibody can function properly both in the context of the chicken B cell and in downstream biodefense applications.